Attempts to make a practical HIV vaccine have been unsuccessful to date. The applicant proposes using anti-idiotype antibody (anti-id) as an HIV vaccine to elicit high titers of group-specific neutralizing antibodies. The principle of this approach is based on idiotype matching, which utilizes anti-ids as surrogates for antigen in an attempt to stimulate specific elements of the B cell repertoire in humans. The applicant will generate and characterize a panel of murine anti-id Mabs against human polyclonal anti-gp120 antibodies. The characterization of anti-id Mabs will be achieved by affinity isolation with individual anti-id Mabs which interact with group specific neutralizing anti-gp120 antibodies for further studies in primates. To identify anti-id Mabs of potential utility in eliciting group-specific neutralizing antibodies, monkeys will be immunized with anti-id Mabs and the sera will be evaluated for neutralizing anti-gp120 antibodies. Evaluation of neutralizing antibodies will be done by measurement of anti-gp120 titer in ELISA and virus neutralization assay using various HIV isolates. In Phase II, protection experiments against viral infection in primates and further evaluation of anti-id Mabs as an HIV vaccine in humans, will be performed.